HTLV infections occur by transmission at mucosal surfaces as well as by systemic inoculation. Therefore, effective vaccines against HTLV-I must elicit protective immune responses at mucosal surfaces as well as in the circulation. Our recent studies have provided the first evidence for the induction of protective immune responses to simian immunodeficiency virus in the genital tract of female rhesus macaques using a microencapsulated vaccine. These results provide the rationale for exploring a similar approach to develop vaccines against HTLV-I. The overall plan of the project to utilize the microcapsule delivery system with formalin- inactivated STLV-I as well as recombinant antigens which should be more suitable for human use. A major goal is the production and characterization of non-infectious particulate antigens expressed by recombinant expression vectors, which should be particularly well suited for microencapsulation. We will compare the results obtained using baculovirus recombinants and vaccinia virus recombinants expressing the envelope and core proteins for the production and purification of VLP's. Alternative cell lines and expression vectors will be employed to obtain particles which contain optimal amounts of envelope proteins. We will incorporate STLV antigens into microspheres consisting of poly (DL- lactide-co-glycolide). These formulations have been shown to have immunopotentiating activity and, when administered to mucosal surfaces, to concurrently induce secretory and mucosal immune responses. A preliminary evaluation of the immunogenicity of the microencapsulated antigens will be carried out in mice. The potential of the microencapsulated vaccine to induce protective immune responses in female rhesus macaques will be determined. Systemic as well as mucosal immune responses will be determined, and protection will be evaluated after challenge with live STLV. Finally we will develop approaches for mucosal immunization with non-replicating plasmids encoding HTLV and STLV antigens. The recent discovery that intramuscular injection of plasmid DNA results in the expression of encoded proteins, and that this approach can be used for protective immunization against viral diseases, provides an attractive approach for induction of long term mucosal immune responses. We will utilize our knowledge of mucosal delivery systems to develop effective procedures for immunization of mucosal inductive sites with plasmid vectors encoding STLV and HTLV antigens.